Ignite Creation Date:
2024-10-26 @ 3:34 PM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06502535
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
None
First Post:
2024-05-14
Brief Title:
Inulin and Nitrates Effects on Vascular Health and Gut Microbiome
Sponsor:
None
Organization:
None
Study Overview
Official Title:
The Effects of Inulin and Inorganic Nitrate on Flow-Mediated Dilation and Gut Microbiome in Adults With Pre-Hypertension and Hypertension
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Previous research has revealed that adults with pre-hypertensive and hypertensive blood pressure levels typically exhibit impaired vasodilation which is a crucial aspect of blood vessel function due to decreased nitric oxide production Flow-mediated dilation FMD is a widely used technique for assessing vasodilation which gauges the capacity of blood vessels to widen in response to increased blood flow Nitrate supplements have been shown to enhance blood vessel function both in the short and long term by elevating nitric oxide NO production Similarly acetate a by-product of fibre digestion has demonstrated anti-inflammatory effects in the gut and may also increase NO production However further investigation is needed to determine whether these two supplements work synergistically to improve FMD responses by augmenting NO production in the human body This study will involve administering inulin plus nitrate supplements to adults aged 45-74 with untreated high blood pressure 120-13980-89 mmHg and 14090 mmHg or higher for a period of 4 weeks followed by a subsequent 4-week period where only inulin supplements are consumed The supplements will be provided in the form of powder to be mixed with water and will be given in a cross-over and counterbalanced order Various measurements including brachial artery function faecal samples blood pressure plasma nitrate and nitrite levels plasma short-chain fatty acid levels red blood cell and whole blood S-Nitrosothiols and salivary nitrate and nitrite levels will be taken at the baseline and after each supplementation period Additionally acute supplementation measurements will be collected on two separate occasions before the start of the longer-term supplement regimen
Detailed Description:
Endothelial dysfunction contributes to the increased cardiovascular risk associated with high blood pressure levels eg 120-13980-89 mmHg and 14090 mmHg or higher and it is considered as an early event in the development of atherosclerotic vascular disease Mechanistically endothelial dysfunction is characterised by a reduced bioavailability of the endothelium-derived molecule nitric oxide NO which is reflected by impaired brachial artery flow-mediated dilation FMD However endothelial dysfunction is largely preventable by its early detection thus approaches that might restore the loss of NO in the body could have obvious therapeutic potential
Consumption of the prebiotic fibre inulin has been shown to increase the fermentation of bacterial-derived metabolites such as acetate by our gut microbiome While increased acetate has local benefits in the gut ie anti-inflammatory lower luminal pH it also has the potential to improve endothelial health Research has shown that acetate can increase NO bioavailability via the activation of the NO synthase pathway by increasing phosphorylation of endothelial NO synthase eNOS a key enzyme in the maintenance of endothelial homeostasis following a 15-day supplementation with inulin Similarly NO is produced following the consumption of nitrate with individual responses being dependent on the basal eNOS activity Therefore individuals with compromised eNOS activity eg pre- and hypertensive might show an augmented response to nitrate supplementation Since both nitrate and inulin supplementations can increase NO production it is possible that their combined ingestion might enhance endothelial function to a greater extent When supplemented in isolation nitrate proved an effective dietary strategy to ameliorate endothelial dysfunction in older and clinical populations For example a 4-week chronic dietary nitrate supplementation 400 mg nitrateday was associated with an increased peak brachial artery FMD of 10 95 CI 03-15 p 0001 which was not evident in the placebo group Similarly following a 4-week dietary nitrate supplementation 400 mg nitrateday brachial artery FMD values increased significantly in the nitrate group compared to the placebo group Unlike nitrate the effects of inulin on brachial artery FMD in humans are yet to be established Preliminary findings demonstrated an enhancement of endothelial function after inulin supplementation in mice These findings were further supported by another study which demonstrated a brachial artery FMD increase of 1 following a 3-month prebiotic supplementation with 12 g fructo-oligosaccharides in clinical patients with less severe endothelial dysfunction
To date no studies that the investigators are aware of have explored the role of nitrate and inulin in combination however based on the above these two nutrients have the potential to work synergistically Therefore the primary aim of this study is to assess whether adding nitrate to inulin during a 4-week chronic supplementation might lead to an increase in brachial artery FMD in middle-aged and youngest elderly adults 45-74 years old with elevated blood pressure and compare this response to inulin supplemented in isolation The secondary aims of this study include brachial artery FMD changes at 4 h post-consumption of a single dose of 15 g inulin and 1300 mg potassium nitrate combined and 15 g inulin supplemented in isolation This study will also explore whether changes in brachial artery FMD following the two supplementations are mediated by potential changes in the gut microbiome composition and diversity that may occur following prebiotics supplementation Further secondary outcomes of the study will investigate differences in plasma nitrate nitrite and short-chain fatty acids SCFAs following both types of supplementation Additionally the study will examine changes in the levels of S-nitrosothiols RSNO in red blood cells and whole blood The study will also compare changes in resting blood pressure between the combined inulin and nitrate supplementation and the inulin-only supplementation
Consumption of the prebiotic fibre inulin has been shown to increase the fermentation of bacterial-derived metabolites such as acetate by our gut microbiome While increased acetate has local benefits in the gut ie anti-inflammatory lower luminal pH it also has the potential to improve endothelial health Research has shown that acetate can increase NO bioavailability via the activation of the NO synthase pathway by increasing phosphorylation of endothelial NO synthase eNOS a key enzyme in the maintenance of endothelial homeostasis following a 15-day supplementation with inulin Similarly NO is produced following the consumption of nitrate with individual responses being dependent on the basal eNOS activity Therefore individuals with compromised eNOS activity eg pre- and hypertensive might show an augmented response to nitrate supplementation Since both nitrate and inulin supplementations can increase NO production it is possible that their combined ingestion might enhance endothelial function to a greater extent When supplemented in isolation nitrate proved an effective dietary strategy to ameliorate endothelial dysfunction in older and clinical populations For example a 4-week chronic dietary nitrate supplementation 400 mg nitrateday was associated with an increased peak brachial artery FMD of 10 95 CI 03-15 p 0001 which was not evident in the placebo group Similarly following a 4-week dietary nitrate supplementation 400 mg nitrateday brachial artery FMD values increased significantly in the nitrate group compared to the placebo group Unlike nitrate the effects of inulin on brachial artery FMD in humans are yet to be established Preliminary findings demonstrated an enhancement of endothelial function after inulin supplementation in mice These findings were further supported by another study which demonstrated a brachial artery FMD increase of 1 following a 3-month prebiotic supplementation with 12 g fructo-oligosaccharides in clinical patients with less severe endothelial dysfunction
To date no studies that the investigators are aware of have explored the role of nitrate and inulin in combination however based on the above these two nutrients have the potential to work synergistically Therefore the primary aim of this study is to assess whether adding nitrate to inulin during a 4-week chronic supplementation might lead to an increase in brachial artery FMD in middle-aged and youngest elderly adults 45-74 years old with elevated blood pressure and compare this response to inulin supplemented in isolation The secondary aims of this study include brachial artery FMD changes at 4 h post-consumption of a single dose of 15 g inulin and 1300 mg potassium nitrate combined and 15 g inulin supplemented in isolation This study will also explore whether changes in brachial artery FMD following the two supplementations are mediated by potential changes in the gut microbiome composition and diversity that may occur following prebiotics supplementation Further secondary outcomes of the study will investigate differences in plasma nitrate nitrite and short-chain fatty acids SCFAs following both types of supplementation Additionally the study will examine changes in the levels of S-nitrosothiols RSNO in red blood cells and whole blood The study will also compare changes in resting blood pressure between the combined inulin and nitrate supplementation and the inulin-only supplementation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None